Persons using assistive technology might not be able to fully access information in this file. For assistance, please send e-mail to: mmwrq@cdc.gov. Type 508 Accommodation in the subject line of e-mail.

Control and Prevention of Rubella: Evaluation and Management of Suspected
Outbreaks, Rubella in Pregnant Women, and Surveillance for
Congenital Rubella Syndrome

Summary

Outbreaks of rubella continue to occur in the United States
despite widespread use of the measles-mumps-rubella (MMR) vaccine.
Throughout the mid- to late-1990s, rubella outbreaks were characterized by
increased numbers of cases among adults born in countries that do not have or
have only recently instituted a national rubella vaccination program. To address
this change in disease epidemiology, CDC's National Immunization Program
(NIP) developed the following recommendations in conjunction with public
health officials in the field. Public health officials should implement
appropriate responses to reports of suspected rubella to determine if an outbreak
exists, evaluate its scope, and implement appropriate control measures.
Health-care providers should be aware of the need for rubella prevention and
control among women of childbearing age and of the appropriate follow-up
for pregnant women exposed to rubella. Comprehensive surveillance
for congenital rubella syndrome should begin during a rubella outbreak.

INTRODUCTION

Since the licensure of the rubella vaccine in 1969, the number of cases of
rubella in the United States has decreased 99%, from 57,686 cases in 1969 to 271 cases
in 1999 (CDC, unpublished data, 2000). The epidemiology of rubella changed in
the 1990s, including shifts in the age distribution, ethnicity, and country of origin
of patients, and in the setting of outbreaks. During the early 1990s, most rubella cases
in the United States occurred among persons aged <15 years; since the
mid-1990s, persons aged >15 years have accounted for most reported cases. In 1999,
adults accounted for 86% of cases, an increase from 41% in 1990, and 73% of persons
with rubella were Hispanic, compared with 4% in 1991 (CDC, unpublished data,
2000). Most of these persons were foreign-born. In recent rubella outbreaks, most
cases occurred among persons from Mexico and Central America. Moreover,
outbreaks occurred predominantly in workplaces and communities; before the
mid-1990s, outbreaks occurred mainly in religious communities, schools, jails, and other
closed environments. Recently, rubella outbreaks have been identified in poultry and
meat processing plants that employ large numbers of foreign-born workers.

The number of cases of congenital rubella syndrome (CRS) has also declined,
and CRS now disproportionately affects infants born to foreign-born women.
During 1997--1999, a total of 21/26 (81%) infants reported with CRS were Hispanic, and
24/26 (92%) were born to foreign-born mothers (CDC, unpublished data, 2000).
Although

information on country of origin was not collected in 1991, a total of 8/42
(19%) infants with CRS were Hispanic. Identifying and managing susceptible
pregnant women who might have been exposed to rubella is challenging, especially
in communitywide outbreaks.

Congenital rubella infection (CRI) encompasses all outcomes associated
with intrauterine rubella infection, including miscarriage, stillbirth, abortion,
combinations of birth defects, or asymptomatic infection in the infant (also known as
infection only) (1). Although serologic testing remains the most available laboratory
method for confirmation, CRI also can be confirmed by reverse transcriptase
polymerase chain reaction (RT-PCR) assays, which detect rubella virus
(2).

Making best use of available technology will help rubella virus surveillance
and ascertainment. For example, molecular typing of rubella virus is available to
identify the origin of the virus as well as which virus strains are circulating. This
information is necessary to document elimination of indigenous transmission.
Universal programs to screen newborn hearing in the United States could help
improve ascertainment of CRS cases because hearing impairment is the most common
single defect associated with CRS (3). Performing serologic testing for rubella on
infants who fail hearing screenings at birth could help identify CRS cases.

This report describes seven steps for evaluating and managing suspected
rubella outbreaks. They were developed by NIP in conjunction with state and local
public health officials based on experience with recent outbreaks in the United States
(4,5). These steps are a) consider a single case of rubella a potential outbreak, b)
confirm the diagnosis, c) conduct case investigations and vaccinate susceptible contacts,
d) enhance active and passive surveillance measures, e) implement rubella
control measures, f) conduct outreach in affected facilities and communities, and g)
develop a plan for preventing future rubella outbreaks. This report also provides
guidelines for evaluating and managing rubella in pregnant and nonpregnant women
and evaluating infants for CRI.

BACKGROUND

Rubella is usually a mild febrile rash illness in adults and children.
Other symptoms include lymphadenopathy, malaise, or conjunctivitis. Arthralgia
and arthritis can occur in <70% of infected adult and adolescent females.
Rare complications are thrombocytopenic purpura, encephalitis, neuritis, and orchitis.
The incubation period for rubella is 12--23 days, and 20%--50% of rubella infections
are asymptomatic. Persons with rubella are most infectious when rash is erupting,
but can shed virus from 7 days before to 5--7 days after rash onset (i.e., the
infectious period).

The most serious consequences of rubella result from infection during the
first trimester of pregnancy. Rubella infection can affect all organs in the developing
fetus and cause miscarriage, fetal death, and congenital anomalies. Up to 90% of
infants born to mothers infected during the first 11 weeks of gestation will develop a
pattern of birth defects called CRS (6); the rate of CRS for infants born to women
infected during the first 20 weeks of pregnancy is 20%. Infants infected with rubella late
in gestation do not exhibit clinical manifestations of CRS. Any infant infected
with rubella in utero can shed virus for
<1 year, sometimes longer (7).

The goal of the rubella vaccination program is to prevent the consequences
of infection during pregnancy. Many countries do not have rubella
vaccination programs or have only recently implemented such programs, and many
adults throughout the world remain susceptible. In 1996, the World Health
Organization (WHO) estimated that 36% of member countries offered routine rubella
vaccination (8). In 1999, WHO estimated that 52% of countries offered routine rubella
vaccination; in the Region of the Americas, 89% of countries used rubella vaccine
(9). Adults in the United States who were born in countries where routine rubella vaccination
was not offered are at higher risk for contracting rubella and having infants with
CRS compared with adults born in the United States. Vaccinating
foreign-born, susceptible adults can be challenging because they might have little or no
contact with the U.S. health-care system. Thus, health-care providers who treat
foreign-born adults should document their rubella immunity with a written record of a
rubella-containing vaccine or by serologic testing. If problems arise in
translating vaccination records from other countries, help is available from the
CDC Immunization Information Hotline at (800) 232-2522 (English) or (800)
232-0233 (Spanish). WHO also has summarized current global vaccination policies
for countries throughout the world (10).

Adequate proof of rubella immunity includes a) written documentation of
receipt of >1 dose of a rubella-containing vaccine administered on or after the first
birthday, b) laboratory evidence of immunity, or c) birth before 1957 (except for women
who could become pregnant). However, during an outbreak, persons born before
1957 should not automatically be considered immune to rubella. Rubella immunity
is defined as a hemagglutination inhibition antibody titer of
>1:8, a hemolysis in gel result of
>10 international units (IU), or an optical density by
enzyme-linked immunoassay (EIA) above the limit set by the manufacturer
(11). Persons who do not meet the above criteria are considered susceptible.

REPORTING

Rubella and CRS became notifiable diseases in the United States in 1966
and 1969, respectively. All 50 states require reporting of rubella and CRS
(12). For information on these requirements, contact local or state health departments.

State and local health departments rely on health-care providers,
laboratory personnel, and other public health workers to report confirmed, probable,
and suspected cases of rubella and CRS so the departments can monitor the
occurrences of these diseases and facilitate appropriate control measures. Health-care
providers and laboratory personnel who suspect cases of rubella, CRS, or congenital
rubella infection only should report them within 24 hours to their local health
department. Health-care providers should not delay reporting suspected cases of rubella,
CRS, and congenital rubella infection only while they wait for laboratory confirmation.

Criteria for Rubella Case Classification

A clinical case of rubella is defined as an illness characterized by a) acute onset
of generalized maculopapular rash; b) temperature >37.2 C (>99.0 F), if measured;
and c) arthralgia/arthritis, lymphadenopathy (usually suboccipital,
postauricular,
and cervical), or conjunctivitis. Case classification for rubella is based on a clinical
case
definition and laboratory criteria for diagnosis
(13). Cases are classified into one of the following categories:

Suspected. Any generalized rash illness of acute onset.

Probable. A case that meets the clinical case definition, has no
or noncontributory serologic or virologic testing, and is not
epidemiologically linked to a laboratory-confirmed case.

Confirmed. A case that is laboratory confirmed or that meets the clinical
case definition and is epidemiologically linked to a laboratory-confirmed case.

Asymptomatic Confirmed. A laboratory-confirmed case in a person who
is asymptomatic that also is epidemiologically linked to a
laboratory-confirmed case clinically consistent with rubella
(14).

Cases are also categorized by importation status:

Indigenous. Any case that cannot be proved to be imported.

State-to-State
Importation. Requires documentation that a person either
had face-to-face contact with a case of rubella outside the state or was out of
the state for the entire period when he or she might have become infected (i.e.,
14--23 days before rash onset).

International
Importation. A case that has its source outside the United
States with onset of rash within 14--23 days of entry into this country.

Laboratory Diagnosis of Rubella

Laboratory diagnosis of rubella requires any one of the following:

A positive serologic test for rubella immunoglobulin M (IgM) antibody.
The preferred testing method for IgM is EIA, using the capture technique;
indirect assays are acceptable (15). IgM antibodies might not be detectable before
4--5 days after rash onset, but they can persist for 6 weeks after rash onset.
If negative results are obtained from a specimen taken before 4--5 days after
rash onset, another specimen should be taken as soon as possible thereafter.
Serum rubella IgM test results that are false positive have been reported in
persons with other viral infections (e.g., acute infection with Epstein-Barr
virus [infectious mononucleosis], recent cytomegalovirus infection, and
parvovirus infection) or in the presence of rheumatoid factor. Patients with
laboratory evidence of recent measles infection are excluded because
concurrent infections are unlikely.

A significant rise in serum rubella immunoglobulin G (IgG) antibody
level between acute- and convalescent-phase titers by any standard serologic
assay. Sera for IgG testing should be collected as early as possible (within 7--10
days) after onset of illness and again >7--14 days (preferably 2--3 weeks) later.

Isolation of rubella virus from nasal, blood, throat, urine, or cerebrospinal
fluid specimens (best results come from throat swabs). Specimens should
be obtained as soon as possible (within 4 days) after rash onset. Efforts should
be

made to obtain clinical specimens for virus isolation from all patients (or
from some patients in each outbreak) at the time of the initial investigation
(14).

Detection of virus by RT-PCR. This process can be used to detect the
presence of rubella virus after growth in tissue culture or directly in clinical specimens.

Specimens submitted for rubella virus isolation or detection by RT-PCR can
also be used for molecular typing. Molecular typing can help determine a) the origin
of the virus, b) which virus strains are circulating in the United States, and c)
whether these strains have become endemic in the United States. Specimens for
molecular typing should be obtained as soon as possible after diagnosis.
Appropriate specimens include throat swabs and cerebrospinal fluid. Specimens for
molecular typing should be sent to CDC as directed by the state health department.
For information on the procedure for obtaining specimens, contact CDC's
National Center for Infectious Diseases, Respiratory and Enterovirus Branch, Measles
Virus Section at (404) 639-3512.

Laboratory Procedures for Persons Exposed to Rubella Who Do Not
Have Rash

Persons exposed to rubella, particularly pregnant women, should be tested
for rubella infection. Asymptomatic rubella infection can be diagnosed by a
positive rubella-specific IgM antibody test or a significant rise in IgG antibody level
between acute- and convalescent-phase tests. The acute-phase IgG serum specimen
should be collected as soon as possible after exposure, whereas the convalescent-phase
IgG specimen should be collected >7--14 days (preferably 2--3 weeks) later.

Case Classification Criteria for Congenital Rubella Syndrome*

CRS results from rubella infection in utero, usually manifests in infancy, and
is characterized by clinical signs or symptoms from the following categories:

Infants with CRS usually present with more than one of these signs or
symptoms. However, infants may present with a single defect. Hearing impairment is the
most common single defect.

Case classification for CRS is based on clinical findings and laboratory criteria
for diagnosis (13). Cases are classified as follows:

Suspected. A case with some consistent clinical findings but not meeting
the criteria for a probable case.

Probable. A case that is not laboratory confirmed and that has any two
findings listed in paragraph a) of the clinical description or one finding from
paragraph a) and one from paragraph b), and lacks evidence of any other etiology.

Confirmed. A clinically consistent case that is laboratory confirmed.

Infection Only. A case that demonstrates laboratory evidence of infection,
but without any clinical symptoms or signs.

CRS cases are also categorized by importation status:

Indigenous Case. Any case that cannot be proved to be imported.

State-to-State
Importation. Requires documentation that the mother either
had face-to-face contact with a case of rubella outside the state or was out of
state for the entire period when she might have become infected (14--23 days
before rash onset or 21 days before conception and during the first 20 weeks
of gestation).

International
Importation. Defined as CRS in a U.S. or non-U.S. citizen
whose mother was outside the United States for the entire period when she may
have had exposure to rubella (21 days before conception and during the first
20 weeks of gestation), or who has known exposure to rubella risks outside
the United States.

Laboratory diagnosis of CRS or congenital rubella infection only requires any
one of the following:

Demonstration of a rubella-specific IgM antibody or infant IgG rubella
antibody level that persists at a higher level and for a longer time than expected
from passive transfer of maternal antibody (i.e., rubella titer that does not drop at
the expected rate of a twofold dilution per month). Approximately 20% of
infected infants tested for rubella IgM might not have detectable titers before age
1 month (L.Z. Cooper, M.D., Columbia University, oral communication,
1998). Thus, infants with symptoms consistent with CRS who test negative soon
after birth should be retested at age 1 month.

Isolation of rubella virus, which can be obtained from nasal, blood,
throat, urine, or cerebrospinal fluid specimens (best results come from throat
swabs). Efforts should be made to obtain clinical specimens for virus isolation
from infants at the time of the initial investigation. However, infants with CRS
and congenital rubella infection only shed virus and are considered infectious for
a prolonged period. Children with CRS should be presumed infectious at
least through age 1 year unless nasopharynx and urine cultures are negative
for virus after age 3 months. Some authorities suggest that an infant with
CRS should be considered infectious until two cultures of clinical
specimens obtained 1 month part are negative for rubella virus.

Detection of virus by RT-PCR. This process can be used to detect the
presence of rubella virus after growth in tissue culture or directly in clinical specimens.

Specimens for molecular typing should be obtained from infants with CRS
as soon as possible after clinical diagnosis. Appropriate specimens include
throat
swabs, cerebrospinal fluid, and cataracts from surgery. Specimens for
molecular typing should be sent to CDC as directed by the state health department.

RECOMMENDATIONS

The seven steps described in this section are recommended for the
evaluation, management, and surveillance of suspected rubella outbreaks (Box). They are
based on recent experience with outbreaks in the United States
(4,5). These recommendations can be used in settings beyond those discussed in this report.

Consider a Single Case of Rubella a Potential Outbreak

Because the incidence of rubella is low in the United States, health
agencies should consider even one case a potential outbreak. Rubella is an infectious
disease for which 20%--50% of cases are asymptomatic, and investigation of an
apparently isolated case could reveal additional cases. Rubella transmission can occur
in congregate settings such as households, workplaces, universities, jails,
or communities. The type and size of the outbreak determines the magnitude of
the response.

Most recent rubella outbreaks were first identified in the workplace. Facilities
that employ many foreign-born workers (e.g., meat or poultry processing plants) are
at greater risk for rubella outbreaks than those with mostly workers born in the
United States. Initial reports can come from on-site health-care providers who have
recently seen rash illness among employees.

Steps to Improve Ascertainment of Rubella Cases in the Workplace

Search on-site medical logs for rash illness and payroll or sick
leave documentation for workers who might have been absent because of illness.

Conduct follow-up interviews with workers who have been sick and contacts
to determine history of recent rash illness.

Steps to Improve Ascertainment of Rubella Cases in the Community

Recently, investigations of workplace outbreaks have revealed spread to
the community. The following steps can help identify cases in the community:

Review the community demographics to determine if there are groups at
high risk for not being vaccinated (e.g., foreign-born persons or members
of religious communities opposed to vaccination).

Because rubella has many symptoms in common with other rash
illnesses, laboratory confirmation is required for case confirmation. Laboratory testing
should be conducted for all suspected cases of rubella. IgM antibodies might not
be detectable before 4--5 days after rash onset. If negative rubella IgM and IgG
results are obtained from specimens taken before 4--5 days, repeat serologic testing
(14).

Conduct Case Investigations and Vaccinate
Susceptible Contacts

Case investigation and identification of contacts should be conducted for
all suspected cases of rubella. In addition, asymptomatic confirmed cases should
be investigated and contacts identified. A descriptive analysis of an outbreak
allows health agencies to focus control measures --- especially vaccination --- on
persons most in need. Cases of rubella occurring in vaccinated persons within 7--10
days after vaccination should be investigated, and specimens should be obtained for
virus isolation to determine if rash is attributable to vaccine virus or wild virus.

Any direct contact with a patient with rubella during the infectious period
(i.e., 7 days before to 5--7 days after rash onset) is defined as exposure. Contact
can include (but is not limited to) living in the same household, attending the same
class or social function, or working side-by-side on a production line. Although
rubella transmission is usually associated with repeated exposure, transmission has
been documented after a single exposure.

Depending on resources available, investigation of contacts of patients
with rubella might need to be prioritized based on the probability of transmission.
The first priority should be persons who share households or persons in a
congregate environment who share space (e.g., side-by-side workers on a production line) with
a patient. The second priority should be persons who share or have
shared environments with a potential for contact (e.g., places of worship, parties,
social gatherings), but who did not knowingly have direct contact with a patient.
If resources allow, investigation of contacts can be extended to geographic areas
or groups at risk where disease has been documented.

Every effort should be made to identify all susceptible pregnant women
who might have been exposed to a patient and test them for rubella immunity.
For example, in a workplace outbreak, pregnant women who have contact with
patients (including coworkers and household contacts) should be evaluated for
rubella immunity. In communitywide outbreaks, health-care workers who treat
pregnant women should be alerted to the outbreak and advised to verify rubella immunity
in pregnant women.

Steps for Locating Exposed Contacts for Further Investigation

Record symptom onset date and infectious period for patients on a calendar
to determine in what setting the exposure might have occurred, where to look
for other exposed persons, and who suspected patients had contact with
during their infectious period. For example, if a person had rash onset January
26, exposure would have occurred 12--23 days earlier (i.e., January 3--14).
The patient would have been infectious from 7 days before to 5--7 days after
rash

onset (i.e., January 19--February 3). Consider asymptomatic confirmed
patients infectious 5--30 days after the last exposure.

Use the calendar to list contacts identified during the infectious period.

Follow up with contacts to assess symptoms of rubella-like illness,
determine susceptibility, and vaccinate susceptible persons without adequate proof
of immunity and who have no contraindications to rubella vaccine.

Continue to investigate contacts of subsequently identified patients.
(See Rubella Prevention and Control Among Women of Childbearing Age
for information on follow-up of pregnant contacts.)

Information That Should be Obtained from Patients With Rubella

Name, address, and telephone number(s) to reach the patient after the
initial interview, if necessary.

Demographic information, including country of origin, length of time in
the United States, and length of time in the state where the rubella diagnosis
was made.

Vaccination status, including the following:
--- Number of doses of rubella vaccine.
--- Dates of vaccination.
--- If not vaccinated, reason for nonvaccination.

Risk factors for disease, including the following:
--- Contact with a probable or confirmed patient or a person with a rash
illness suspected of being rubella.

--- Transmission setting (e.g., day care center, school, workplace, place
of worship, athletic event, or other congregate or social gathering).
--- Relationship to outbreak (i.e., whether case is sporadic or part of
an identified outbreak).
--- Travel history.
--- Contact with others who have recently traveled (i.e., import
status [indigenous, state-to-state, or international], state name, and country
name [and state within the country]).

Information regarding contacts during the infectious period (i.e., 7 days
before to 5--7 days after rash onset), including the following:
--- List of persons with household contact (e.g., residents and others with
close contact in the home) and persons with contact in a congregate
environment with shared space.
--- List of women who are pregnant who have had contact with a patient
with rubella.
--- Rubella symptoms (e.g., rash, fever, lymphadenopathy) of contacts.
--- Place of employment of contacts.

Vaccination status, including the following:
--- Number of doses of rubella vaccine.
--- Dates of vaccination.
--- If not vaccinated, reason for nonvaccination.

Risk factors for disease, including the following:
--- Contact with a probable or confirmed patient or a person with a rash
illness suspected of being rubella.
--- Transmission setting (e.g., day care center, school, workplace, place
of worship, athletic event, or other congregate or social gathering).
--- Relationship to outbreak (i.e., whether case is sporadic or part of
an identified outbreak).
--- Travel history.
--- Contact with others who have recently traveled (i.e., import
status [indigenous, state-to-state, or international], state name, and country
name [and state within the country]).

Information regarding contacts during the infectious period (i.e., 7 days
before to 5--7 days after rash onset), including the following:
--- List of persons with household contact (e.g., residents and others with
close contact in the home) and persons with contact in a congregate
environment with shared space.
--- List of women who are pregnant who have had contact with a patient
with rubella.
--- Rubella symptoms (e.g., rash, fever, lymphadenopathy) of contacts.
--- Place of employment of contacts.

For this step, outbreak investigators should institute surveillance
measures designed to identify cases prospectively, as well as any cases with rash onset
that preceded the first identified case. Because some persons with rubella do not
have rash, these measures should use a broader definition of suspected cases (e.g.,
fever with lymphadenopathy or arthralgia/arthritis in adult women) in areas where
rubella cases have been confirmed. Broadening the case definition and
investigating suspected cases could lead to more complete ascertainment.

Components of Surveillance for Rubella in an Outbreak Setting

Identify health-care providers and facilities serving populations at risk
and involve them in surveillance.

Identify workplaces with large numbers of persons who might lack
rubella immunity and involve them in surveillance.

Identify day cares, schools, places of worship, and community
organizations (particularly in neighborhoods where many residents might lack
rubella immunity) and involve them in surveillance.

Promote awareness among health-care providers that rubella and CRS
still occur in the United States among certain groups that lack rubella immunity.

Distribute written guidelines instructing health-care providers to
obtain appropriate serology and specimens and to notify health departments of
all suspected rubella cases.

Establish routine contact (e.g., daily or weekly) with hospitals, doctors'
offices, clinics, schools, and laboratories to obtain reports of persons with rash
illness or other symptoms indicative of rubella.

In addition to prospective surveillance, retrospective case finding should
be conducted for 6 weeks (i.e., two incubation periods) before the first identified case.
If evidence indicates that the outbreak was in progress during this time,
retrospective case finding should continue until no further cases are identified.

During a rubella outbreak, the following control measures should be taken:

Isolate patients for 5--7 days after rash onset.

Identify and vaccinate susceptible persons who have no contraindications
to rubella vaccine.

Ensure that pregnant women who are exposed to rubella and do not
have adequate proof of immunity are serologically evaluated for rubella-specific
IgM and IgG antibodies (see Laboratory Diagnosis of Rubella).

Counsel susceptible pregnant women regarding the risks for
intrauterine rubella infection and recommend that they restrict their contact with
persons with confirmed, probable, or suspected rubella for
>6 weeks (two incubation periods) after rash onset in the last identified patient. Pregnant women
should also be advised to avoid activities where they might be exposed to rubella for
6 weeks (two incubation periods) after the onset of symptoms of rubella in
the last patient for whom rubella cannot be ruled out to minimize their chances
of

coming in contact with persons with symptomatic or asymptomatic
rubella infection (see Rubella Prevention and Control Among Women of
Childbearing Age).

Control Measures for Specific Settings

Congregate Environments. Congregate environments include households,
jails, day cares, schools, military settings, workplaces, places of worship, athletic
events, and other social gatherings. Control measures recommended for these settings
are as follows:

Refer persons without adequate proof of rubella immunity for vaccination
or offer on-site vaccination clinics. After vaccination, these persons no
longer need to restrict contact. The exception is health-care workers (see
Health-Care Settings).

Isolate patients during their infectious period (i.e., 5--7 days after rash
onset). Recommend that patients restrict contact with pregnant women and
persons without adequate proof of rubella immunity for 5--7 days after rash onset.

Recommend for day cares and schools that persons exempt from
rubella vaccination for medical, religious, or other reasons be excluded
from attendance for 3 weeks after onset of rash in the last reported patient in
the outbreak setting.

Recommend that all susceptible persons who were not vaccinated as part
of the control efforts (e.g., those who refused vaccination or who
had contraindications to vaccine) minimize contact with patients for 5--7 days
after rash onset.

Recommend that susceptible pregnant women not attend activities,
particularly in the first trimester of pregnancy, where they might be exposed to rubella
for >6 weeks (two incubation periods) after the onset of symptoms of rubella in
the last patient for whom rubella cannot be ruled out to minimize their chances
of coming in contact with persons with asymptomatic rubella infection.

Health-Care Settings. Health-care settings include hospitals, doctors'
offices, clinics, nursing homes, and other facilities where patients receive subacute
or extended care. Control measures recommended for these settings include
excluding and vaccinating health-care workers without adequate evidence of
immunity, particularly in settings where pregnant women could be exposed.

All persons who work in health-care facilities or who have contact with
any patients should be immune to rubella. Any exposed health-care worker who does
not have adequate evidence of immunity should be excluded from duty beginning
7 days after exposure to rubella and continuing through either a) 21 days after
last exposure or b) 5--7 days after rash appears. Susceptible, exposed
health-care workers who are vaccinated should be excluded from direct patient care for 23
days (i.e., the longest incubation period) after the last exposure to rubella because
no evidence exists that postexposure vaccination is effective in preventing
rubella infection in persons already infected at the time of vaccination. Because birth
before 1957 does not guarantee immunity, health-care facilities should strongly
recommend
a dose of MMR vaccine to workers born before 1957 who do not have
serologic evidence of immunity.

Communitywide Rubella Outbreaks. When communitywide outbreaks occur,
the following steps are recommended:

Attempt to ensure proper isolation procedures for all patients. In general,
any person exposed to a patient with rubella or CRS who cannot demonstrate
proof of immunity should receive vaccine or restrict contact with patients with
rubella or CRS.

Make every effort to identify and test all exposed pregnant women.
In communitywide outbreaks, health-care workers who treat pregnant
women should be alerted to the outbreak and advised to verify rubella immunity
in pregnant women (see Rubella Prevention and Control Among Women
of Childbearing Age).

Conduct Outreach in Affected Facilities and Communities

Outreach activities should begin during the outbreak investigation and
should convey the seriousness of rubella infection and the importance of rubella
vaccination and other control efforts. Outreach activities also provide an opportunity to
reinforce the importance of persons seeking medical advice for rubella-like illnesses and
of health-care workers reporting rubella.

Workplace

In the workplace, outreach activities should focus on educating workers
and employers regarding rubella and its consequences, using such strategies
as educational sessions, flyers, letters, and E-mail. Stress that persons who work in
a place where an outbreak is in progress and who live with or have contact
with someone who is pregnant should be vaccinated unless known to be immune.

Community

A communitywide outbreak can be most effectively contained if public
health agencies form partnerships with community leaders, health-care providers,
and groups with a history of effective community involvement. These persons can act
as liaisons between public health agencies and the community. Outreach activities
in the community should include the following:

Identifying persons in the community who can serve as liaisons between
public health agencies and the local population (e.g., community activist
groups, members of the foreign-born community, health-care workers who
treat migrant populations, and leaders in places of worship).

Training these liaisons on the current epidemiology and clinical symptoms
of rubella, as well as laboratory testing methods (for health-care
providers). Stress the importance of vaccinating persons who are susceptible to
rubella, particularly persons who live in households with pregnant women or
any women of childbearing age.

Working with liaisons to develop targeted education messages and
materials that address community members' beliefs regarding health care.
Distribute messages and materials where community members who are at risk are
likely to have access to them.

Encouraging liaisons to participate in surveillance activities (e.g., they could
be aware of persons in community organizations who have missed
activities because of illness).

Establishing vaccination sites in areas frequented by the local population
(e.g., places of worship, day labor pick-up sites, worksites, or places where
special celebrations are held) and providing counseling on the importance of
rubella vaccination. Bilingual personnel might be needed to serve as counselors
and investigators at these sites.

Develop a Plan for Preventing Future Rubella Outbreaks

Prevention of future rubella outbreaks includes ensuring high levels of
rubella immunity, vaccinating susceptible persons, maintaining rubella and CRS
surveillance and reporting, and preparing an appropriate and rapid response when a case
of rubella is identified. To make the most effective use of resources to prevent CRS
and control rubella, state and local health authorities might want to identify and
prioritize counties and communities in order of decreasing risk and conduct vaccination
or education campaigns accordingly. Depending on cost and available resources,
health department personnel might decide to target all counties and communities in
the state or limit the campaigns to those at highest risk for rubella outbreaks based
on known or suspected susceptibility patterns and the likelihood of introduction
of rubella into the community. Based on the current epidemiology of rubella,
counties most at risk appear to be those with substantial numbers of adolescents and
young adults born and raised in countries that do not have a history of routine
rubella vaccination.

All states should conduct activities for the prevention of
CRS or CRI, including the following:

Identifying women of childbearing age at risk for rubella infection and
ensuring immunity in women by enhancing existing programs (e.g., prenatal testing
and postpartum vaccination). Approximately 50% of CRS cases could be
prevented through postpartum vaccination of women known to be susceptible
to rubella (16).

Ensuring that MMR vaccine is available to providers through the Vaccines
for Children (VFC) program or the 317 Immunization Grant Program (under
the Public Health Service Act). For more information on these programs,
contact

In addition, states that have had recent rubella outbreaks or a recent
indigenous CRS case or that have identified populations at high risk for rubella outbreaks
might want to emphasize rubella control as well as CRS prevention through the
following activities:

Ensuring immunity among all persons (male and female), especially
foreign-born persons who are not likely to have received rubella vaccination.

At workplaces where recent rubella outbreaks have occurred or high numbers
of persons at risk for rubella are employed, state health departments should

educate management and workers regarding the risks for rubella and CRS.

recommend that all employees susceptible to rubella receive MMR vaccine.

recommend that rubella immunization be provided in the workplace.
Some states might consider conducting projects to demonstrate the feasibility
of rubella immunization in the workplace.

ensure that workers who are vaccinated receive personal immunization
record cards.

ensure that family members and close personal contacts of susceptible
workers are referred to the health department or other provider for immunization.

In communities that have had recent rubella outbreaks or where large numbers
of persons at risk for rubella reside, state health departments should

identify leaders in communities at risk to serve as spokespersons for
rubella control and CRS prevention programs;

work with community groups (i.e., civic or faith-based organizations) to
conduct education programs and vaccination campaigns;

encourage employers to establish a rubella screening and vaccination
program for all current and new employees; and

provide necessary vaccines for group members at risk identified in
public health clinics.

alert other state health departments of rubella outbreaks, particularly
those with evidence of state-to-state importation.*

VACCINE

This section summarizes information available in the most recent ACIP
statement on MMR vaccination (17). In the United States, most rubella vaccination
is administered as part of the MMR vaccine. Approximately 21--28 days are required
for development of protection following vaccination.

Persons generally are presumed immune to rubella if they a) have
documentation of vaccination with >1 dose of MMR or other live, rubella-containing
vaccine administered on or after the first birthday, b) have laboratory evidence of
immunity, or c) were born before 1957 (except women who could become
pregnant). Susceptible adults born after 1957 who do not have a medical
contraindication should receive >1 dose of MMR vaccine for protection against rubella and two
doses >1 month apart if at high risk for exposure to measles
(17). Birth before 1957 is not acceptable evidence for rubella immunity for women who could become pregnant.

Contraindications and Precautions

Following is a summary of contraindications and precautions for
administration of MMR vaccine. For more detailed information, consult the most recent
ACIP statement on MMR vaccination (17).

Allergic Reactions

MMR vaccine should not be administered to persons who have
experienced severe allergic reactions to a previous dose of a rubella-containing vaccine or to
a vaccine component (e.g., gelatin or neomycin). Allergy to egg is not
a contraindication.

Pregnancy

MMR vaccine should not be administered to women known to be pregnant
or attempting to become pregnant. Because of the theoretical risk to the fetus,
women should be counseled to avoid becoming pregnant for 3 months after receipt of
a rubella-containing vaccine (18). If a pregnant woman is vaccinated or
becomes pregnant within 3 weeks after receipt of vaccine, she should be counseled
regarding the theoretical basis of concern for the fetus. However, receipt of
rubella-containing vaccine during pregnancy should not ordinarily be a reason to consider
termination of pregnancy. Women who are susceptible to rubella and not vaccinated
because they are pregnant or might become pregnant within the next 3 months should
be advised regarding the potential risk for CRS and the importance of being
vaccinated as soon as they are no longer pregnant
(17).

From January 1971 through April 1989, CDC followed to term 321 known
rubella-susceptible women who were vaccinated within 3 months before or 3 months
after conception. Ninety-four women received HPV-77 or Cendehill vaccines, one
received vaccine of unknown strain, and 226 received RA 27/3 vaccine (the only
rubella vaccine presently used in the United States). None of the 324 infants born to
these mothers had malformations compatible with CRI, but five had evidence of
subclinical rubella infection, two of whom were exposed to RA 27/3 vaccine
(17). Based on these data, the estimated risk for serious malformations attributable to RA 27/3
vaccine ranges from zero to 1.6% (17). Breast-feeding is not a contraindication to
receiving MMR vaccine.

Immunodeficiency

MMR vaccine should not be administered to persons with
severe immunodeficiency from any cause. Persons with mild immunosuppression
(e.g.,
from asymptomatic human immunodeficiency virus [HIV] infection or short-term
or low-dose steroid use) may be vaccinated.

Illness

Health-care providers should evaluate whether to administer MMR vaccine to

persons with history of thrombocytopenia. The decision to vaccinate
should depend on the benefits of immunity to measles, mumps, and rubella
compared with the risks for recurrence or exacerbation of thrombocytopenia either
after vaccination or during natural infection with measles or rubella.

persons who have received high doses of immunoglobulins. Recent
evidence indicates that high doses of immunoglobulins can inhibit the immune
response to rubella vaccine for >3 months.

Vaccine Information Statements (VIS)

The National Childhood Vaccine Injury Act (NCVIA) requires all
health-care providers in the United States who administer MMR vaccine to provide a copy of
the relevant VIS to either an adult vaccinee, or in the case of a minor, to a parent or
legal representative (18). Health-care providers are not required to obtain the signature
of the patient, parent, or legal representative acknowledging receipt of the
VIS. However, to document that the VIS was given, health-care providers must note
in each patient's permanent medical record at the time a VIS is provided the
date printed on the VIS and the date the VIS is administered to the vaccine
recipient, parent, or legal representative. NCVIA also requires that health-care providers
note the following information in the patient's permanent medical record:

The date of administration of the vaccine.

The manufacturer and lot number of the vaccine.

The name and address of the health-care provider administering the
vaccine (i.e., the address where the record is kept; if vaccinations are administered in
a shopping mall, for example, the address should be the clinic where
the permanent record will reside).

Reporting of Adverse Events

The National Vaccine Injury Act of 1986 requires physicians and other
health-care providers who administer vaccines to maintain permanent immunization records
and to report occurrences of adverse events for selected vaccines
(17). Serious adverse events (i.e., all events requiring medical attention), regardless of whether they
are suspected to have been caused by vaccine, should be reported to the
Vaccine Adverse Event Reporting System (VAERS). VAERS forms and instructions
are available in the FDA Drug Bulletin and the
Physicians' Desk Reference or by calling the 24-hour VAERS information recording at (800) 822-7967.

RUBELLA PREVENTION AND CONTROL AMONG WOMEN OF CHILDBEARING AGE

Guidelines for rubella prevention and control among women of childbearing
age differ depending on the likelihood of exposure to rubella. Identifying women
who could have been exposed is critical so they can receive appropriate testing
and follow-up. Guidelines for testing and follow-up for all women of childbearing
age, pregnant women for whom rubella exposure is unlikely, and pregnant women
who might have been exposed to rubella are outlined in the following sections.

All Women of Childbearing Age

Health-care providers who treat women of childbearing age should
routinely determine rubella immunity and vaccinate those who are susceptible and
not pregnant. Proof of immunity can be either a verified record of vaccination or
a positive IgG antibody serologic test. Rubella-susceptible women who a) do not
report being pregnant, b) are not likely to become pregnant in the next 3 months, and c)
do not have other contraindicating conditions should be vaccinated. Before
vaccination, each patient should be counseled to avoid pregnancy for 3 months after
vaccination because of the theoretical risk for vaccine virus affecting the fetus. Because
routine pregnancy screening is not recommended before rubella vaccination,
patients should be counseled regarding the theoretical risk to the fetus from
inadvertent vaccination of a pregnant woman.

Pregnant Women Without Likely Exposure

Even when no outbreaks have been reported and no rubella exposure
has occurred, health-care providers should routinely conduct a rubella IgG test for
all pregnant women at the earliest prenatal visit. A positive rubella IgG antibody
test indicates rubella immunity, and health-care providers can assume that immunity
was acquired before pregnancy. Women who are found to be susceptible should
be monitored for signs of rubella during pregnancy and vaccinated
postpartum. Susceptible pregnant women should be advised to avoid contact with persons
with rash illness.

An IgM test should not be used to determine rubella immune status; IgM is
used to diagnose acute and recent rubella infection. The TORCH (i.e.,
toxoplasmosis, rubella, cytomegalovirus, and herpes) panel includes a test for rubella IgG
antibodies as well as a test for rubella IgM antibodies. Because of the potential for
false-positive IgM results, a TORCH panel should not be used to determine rubella
immunity. Rubella IgM testing should be performed on pregnant women who report
symptoms of rubella or susceptible pregnant women who might have been exposed to
rubella to rule out acute or recent infection.

Screening and Follow-Up of Pregnant Women Who
Might Have Been Exposed to Rubella

Because the consequences of rubella infection during pregnancy are
serious, every effort must be made to identify all women of childbearing age exposed to
a
person with confirmed, probable, or suspected rubella. Women found to
be susceptible and not pregnant should be vaccinated as outlined previously (see
All Women of Childbearing Age). Susceptible household contacts of pregnant
women should also be vaccinated.

All exposed pregnant women should be screened to determine if they a)
were infected during pregnancy, b) are susceptible, or c) were immune before
pregnancy. Because of the seriousness of CRI, immunity must be documented by a
verified, dated record of a positive serologic test. Pregnant women without
documented immunity should be tested for the presence of rubella IgG and IgM antibodies
as outlined in this section. Identifying susceptible pregnant women is critical, so
they can be isolated from further exposure, monitored for infection, and
vaccinated postpartum. Pregnant women with evidence of infection during pregnancy should
be evaluated to verify rubella infection and determine gestational age at time
of infection, if possible, to assess the possibility of risk to the fetus.

Immunoglobulin (IG) does not prevent rubella or mumps infection after
exposure and is not recommended for that purpose
(18). Administration of IG after exposure
to rubella will not prevent infection or viremia, but might modify or suppress
symptoms and create an unwarranted sense of security. Therefore, IG is not recommended
for routine postexposure prophylaxis of rubella in early pregnancy or any
other circumstance. Infants with congenital rubella have been born to women
who received IG shortly after exposure. Administration of IG should be considered only
if a pregnant woman who has been exposed to rubella will not consider termination
of pregnancy under any circumstances. In such cases, intramuscular administration
of 20 mL of IG within 72 hours of rubella exposure might reduce --- but will
not eliminate --- the risk for rubella.

During an outbreak, the following steps should be taken to evaluate and follow
up with pregnant women who had contact with a person with confirmed, probable,
or suspected rubella:

Use documented serologic test results to verify immunity. If
unavailable, conduct rubella IgG and IgM antibody testing regardless of symptom
history. Pregnant women who are exposed to rubella and who do not
have documented proof of immunity should be tested for rubella-specific
IgM antibodies to identify recent infection. Because 20%--50% of rubella cases
are asymptomatic, this testing policy is crucial to assess the possibility of risk
to the fetus. Another way to identify recent infection is to detect a significant
rise in paired IgG serum. A single positive IgG test indicates rubella immunity,
but does not give information regarding the timing of the infection. However,
a significant rise in IgG antibody (determined by testing paired sera) or
positive IgM antibody test indicates recent infection.

Recommend restricting activities to avoid exposure while waiting for
serologic test results. During this time, pregnant women should be excluded
from activities (e.g., work or school) that present the possibility of exposure
to persons with confirmed or suspected cases of rubella. Pregnant women
found to be susceptible to rubella should avoid these settings for 6 weeks
(two incubation periods) after the onset of symptoms of rubella in the last patient
for whom rubella cannot be ruled out.

Evaluate exposed pregnant women with positive IgG titers and negative IgM
to determine if they acquired immunity before pregnancy or infection
during pregnancy. Women without previously documented immunity who
were exposed during pregnancy and >6 weeks before IgM testing could test
negative for IgM antibodies, which are normally not detectable >6 weeks after
infection. Thus, a negative rubella IgM antibody assay does not rule out infection
during pregnancy. The dates of the pregnancy, possible exposures, test(s), and
history of rash illness should be considered in assessing the possibility of risk to
the fetus.

Evaluate pregnant women with confirmed rubella to assess risk to the
fetus. Rubella infection during the first 3 months of pregnancy is associated with
the greatest risk for CRI, and up to 90% of infants born to mothers infected
during the first 11 weeks of gestation will develop CRS. Infection late in the first half
of pregnancy is more likely to result in hearing impairment and less likely to
be associated with other defects. Although not likely to result in CRS,
rubella infection late in pregnancy can result in congenital rubella infection only.

Pregnant women with negative IgG and negative IgM on first testing should
be retested in 10--14 days; the first specimen should be reanalyzed along with
the second specimen. A significant rise in IgG or positive IgM indicates
recent infection. If a susceptible pregnant woman continues to be directly exposed
to rubella, repeat tests of paired sera in 10--14 days to determine if
infection occurs, then every 3--4 weeks if exposure continues. Testing can be
performed earlier if pregnancy outcome might be influenced. Evaluate the infant
on delivery for signs of CRS, and vaccinate the mother postpartum.

Recommend restricting activities for susceptible women (i.e., those
without detectable IgG and IgM antibodies), obtain follow-up serologic testing,
and vaccinate after delivery. Susceptible pregnant women should be excluded
from activities (e.g., work or school) that present the possibility of exposure
to persons with confirmed or suspected cases of rubella. Pregnant women
found to be susceptible should avoid these settings for 6 weeks (two
incubation periods) after the onset of symptoms of rubella in the last patient for
whom rubella cannot be ruled out. Household contacts or other ongoing
contacts without documented rubella immunity should be vaccinated.

Evaluate asymptomatic, exposed pregnant women with documented history
of previous rubella immunity. Rubella reinfection is rare but has
been documented (19--22). Women with documentation of previous
rubella immunity who are exposed to rubella during pregnancy should consult
their physicians. After discussing the potential for reinfection, physicians
might recommend acute- and convalescent-phase IgG antibody testing or an
IgM antibody test to document whether reinfection has occurred. However,
the potential for false-positive IgM tests exists, and the potential risks and
benefits of testing should be considered.

Counsel pregnant women with documentation of previous immunity to
seek medical attention promptly if rubella-like symptoms appear. Any
pregnant woman with documented immunity and rubella-like symptoms should
be

immediately evaluated by a physician to diagnose the symptoms and
ensure the health of the mother and fetus.

SURVEILLANCE FOR CONGENITAL RUBELLA SYNDROME

Consequences of CRI during pregnancy include abortion, miscarriage,
stillbirth, and a pattern of birth defects called CRS. The most common congenital
defects related to CRS are cataracts, heart defects, hearing impairment, and
developmental delay. Other less specific signs and symptoms of CRS include
purpura, hepatosplenomegaly, jaundice, microcephaly, meningoencephalitis, and
radiolucent bone disease.

Pregnant women with known rubella exposure should receive follow-up
care. Surveillance for CRI and CRS should be implemented when confirmed or
probable rubella cases are documented in a setting where pregnant women might have
been exposed. The following steps are recommended to achieve these goals:

Follow the outcome of pregnancy for pregnant women with confirmed
or suspected rubella infection and for susceptible pregnant women with
rubella exposure. A state or local registry of pregnant women with confirmed
or suspected rubella should be established to record pregnancy outcomes
(e.g., abortion, stillbirth, congenital rubella-associated defects) and
laboratory evaluation of infants. Because hearing impairment, cataracts, and heart
defects are common among infants with CRS, hearing and vision evaluations
for infants born to susceptible, pregnant women exposed to rubella could
help identify cases and aid early diagnosis and intervention.

Educate and heighten awareness among health-care providers.
Health-care providers in the area of an outbreak should be made aware of the potential
for CRS births in their facilities and given information regarding the
physical manifestations of CRS and appropriate laboratory testing for infants
with suspected CRS. The classic presentation for CRS is cataracts,
hearing impairment, and congenital heart disease (especially patent ductus
arteriosus or peripheral pulmonic stenosis). Some conditions associated with CRS
(e.g., hearing impairment and developmental delay) might not be apparent at birth.

The following steps are recommended for follow-up and surveillance for CRS
and congenital rubella infection only cases:

Discuss appropriate isolation procedures for infants with CRS and
congenital rubella infection only with health-care providers. Only persons immune
to rubella should have contact with these infants. Children with CRS should
be presumed infectious at least through age 1 year unless nasopharynx and
urine cultures are negative for virus after age 3 months. Some authorities
suggest that an infant with CRS should be considered infectious until two cultures
of clinical specimens obtained 1 month part are negative for rubella virus.

Use universal newborn hearing screening programs to help detect CRS,
where available. Approximately 50% of states have such programs, some of
which use a combination of evoked otoacoustic emissions and auditory
brainstem response to identify hearing impairment in newborns. Because
hearing

impairment is the most common single defect associated with CRS,
newborns who fail hearing screening tests should be tested for rubella-specific
IgM antibodies to rule out CRS.

Report all CRS and congenital rubella infection only cases to the state
health department as soon as they are suspected, even though
laboratory confirmation might be pending. State health departments should then
report cases to CDC's Rubella Activity at (404) 639-8230. Cases are then entered
into the National Congenital Rubella Syndrome Registry. The following data
are epidemiologically important and should be collected during case
investigations (additional information can be collected at the direction of the state
health department):
--- Demographic information.
--- Maternal history, including a) date of rubella vaccination(s), b) dates
and results of previous serologic tests for rubella immunity, c) history
or documentation of rubella infection during pregnancy, d) history
of pregnancies inside and outside the United States, e) country of birth
and length of residence in the United States, and f) history of exposure to
rubella and travel.
--- Clinical details (e.g., cataracts, hearing impairment, developmental
delay, type of congenital heart defect, meningoencephalitis, microcephaly).
--- Laboratory information, including types and results of laboratory
testing performed on both mother and child.

Recommend consultation with specialists for infants with CRS, as
appropriate, based on clinical manifestations.

CONCLUSION

Rubella outbreak control is essential for eliminating indigenous rubella
and preventing CRS and CRI. Strategies for rubella outbreak control include
defining target populations for rubella vaccination, ensuring that susceptible persons
within the target populations are vaccinated rapidly (or excluded from exposure if
a contraindication for vaccination exists), and maintaining rubella and
CRS surveillance (18). Control measures should be implemented as soon as a case
of rubella is identified. Maintaining control measures is essential when
pregnant women are possible contacts of patients with rubella. Susceptible pregnant
women who are exposed to rubella should be thoroughly evaluated for possible
rubella infection.

CDC. Measles, mumps, and rubella---vaccine use and strategies for elimination
of measles, rubella and congenital rubella syndrome and control of
mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP).
MMWR 1998;47(No. RR-8).

* Most of the wording in this section comes directly from the case definitions developed
by CDC and the Council of State and Territorial Epidemiologists (CSTE) (CDC. Case
definitions for infectious conditions under public health surveillance. MMWR 1997;46[No. RR-10]:30).

* Special Supplemental Nutrition Program for Women, Infants, and Children.

DisclaimerAll MMWR HTML versions of articles are electronic conversions from ASCII text
into HTML. This conversion may have resulted in character translation or format errors in the HTML version.
Users should not rely on this HTML document, but are referred to the electronic PDF version and/or
the original MMWR paper copy for the official text, figures, and tables.
An original paper copy of this issue can be obtained from the Superintendent of Documents,
U.S. Government Printing Office (GPO), Washington, DC 20402-9371; telephone: (202) 512-1800.
Contact GPO for current prices.

**Questions or messages regarding errors in formatting should be addressed to
mmwrq@cdc.gov.